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Dr. Francis Collins talks about aging biology at the Geroscience Interest Group seminar

July 13, 2012

On July 12, all of the seats in the Masur Auditorium were filled for the meeting of the NIA’s Geroscience Interest Group (GSIG), a newly formed trans-NIH interest group focused on the premise that aging biology is at the base of many of the chronic diseases that form significant portions of the research portfolios of most NIH Institutes and Centers.

The full house was no surprise: The featured speaker was NIH Director Dr. Francis Collins. Dr. Collins described his research on Hutchinson Gilford Progeria Syndrome (HGPS), as well as its relevance to understanding normal aging. “It has been an amazing journey, moving very rapidly from gene discovery to clinical trials,” said Dr. Collins. HGPS is an extremely rare disorder characterized by exceptionally accelerated aging, leading to premature death at an average age of 13 years, usually from cardiovascular complications.

Dr. Collins’ journey in this field started when, as a young physician, he was put in charge of Meg, a “real spitfire” of a young lady, he says, who was affected by the disease. His interest in HGPS was reawakened many years later when he was approached by Dr. Leslie Gordon of the Progeria Research Foundation, whose son Sam also has HGPS.

Sparked by his encounter with Sam and others with HGPS, Dr. Collins’ laboratory put their interest into action, and in 2003 identified a single point mutation responsible for the syndrome, a silent mutation (G608G) in the gene coding for lamin A, a structural component of the nuclear envelope. Further molecular studies revealed that the mutation caused increased activation of a silent splice site, leading to the production of a truncated lamin A molecule termed progerin. Based on detailed knowledge of the biology of lamins and on his own research, Dr. Collins and his team were able to rapidly move the field toward translation so that within 5 years, a clinical trial for HGPS was begun, and, today, a second clinical trial is currently being considered.

This is good news for the affected children and their families, who now have hope for management of HGPS. But the interest in HGPS goes beyond the disease itself. While viewed as an accelerated aging syndrome, many investigators in the aging research community have not thought these syndromes to faithfully represent normal aging. Aware of this view, Dr. Collins gave evidence of the potential for HGPS research to inform basic aging research. Not only is progerin produced by normal cells during aging, he noted, but abnormal splicing appears to be a common feature of aging, especially in cells that reach senescence via telomere loss.

Dr. Collins is currently collaborating with NIA Director Dr. Richard Hodes, an expert in telomere biology who conducts research in his laboratory at the National Cancer Institute, to further pursue this area of research.

“The seminar demonstrated the power of genetic and basic biology approaches not only to provide hope to individuals with rare diseases, but also to inform more common issues, including normal aging. I’m excited about the collaboration our labs have recently initiated,” said Dr. Hodes.

During a discussion with the GSIG Executive Committee after the seminar, both Drs. Collins and Hodes reinforced their hope that this group could become a major force in trans-NIH efforts.

“Aging biology has reached a tipping point for research,” said Dr. Felipe Sierra, GSIG founder and director of NIA’s Division of Aging Biology. “We have recent evidence that the aging process is malleable and it has been observed in several animal models that—when aging is delayed—so are the diseases and disabilities that normally accompany aging.”